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Biomedical subjects

R Whittaker

Publications and source records attributed to R Whittaker.

At least 19 recordsLinked to original sources
PubMed2000

Tris lipidation: a chemically flexible technology for modifying the delivery of drugs and genes.

1. One of the major challenges in the development of pharmaceuticals is their formulation with other materials to give them the desired bioavailability profile when administered into the body. 2. We have developed a flexible platform technology (Tris lipidation) to simply and effectively alter the lipophilicity of drugs. As implied by the name, the technology uses the common buffer Tris as a linker between the drugs of interest and a domain of variable hydrophobicity. 3. We demonstrate, using a mouse melanoma model, that Tris-lipidated conjugates of the widely used cytotoxic and anti-inflammatory drug methotrexate (MTX) display enhanced potency in the local treatment of tumours and reduced systemic toxicity when compared with the unconjugated drug. 4. With genes now being predicted to be the pharmaceuticals of the future, we show that Tris-lipidated cationic peptides can efficiently deliver DNA into (transfect) cells in culture. Furthermore, by comparing the abilities of variants of these Tris-based cationic lipids to transfect cultured cells, we demonstrate that modifications made to variable regions of Tris-lipidated compounds can dramatically alter their delivery profiles.

Animals↗
PubMed1999

Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: correlation with up-regulation in epithelial ovarian cancer.

Abnormalities in the function of receptor tyrosine kinases (RTKs) have been demonstrated to be important in the pathogenesis of cancer. H-Ryk, a new member of the RTK family, is an unusual RTK in that it is catalytically inactive because of amino acid substitutions of conserved residues in the catalytic domain. We show by immunohistochemistry that it is expressed in the epithelium, stroma, and blood vessels of normal tissues. Evaluation of a panel of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) was performed. H-Ryk was overexpressed in borderline and malignant ovarian tumors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observation, overexpression of H-Ryk in the mouse fibroblast cell line NIH3T3 induces anchorage-independent growth and tumorigenicity in nude mice. This implies that overexpression of the receptor can be transforming and may therefore be significant in the pathogenesis of ovarian cancer.

3T3 Cells↗
PubMed1998

Re-framing the representation of women in advertisements for hormone replacement therapy.

This article examines and presents examples of contemporary advertising within the medical and health professions that continue the process and organisation of knowledge about women and their reproductive bodies. It draws on feminist and poststructural perspectives to inform a critical evaluation of the visual representations of menopausal women and hormone replacement therapy. These representations work to construct certain definitions of the feminine that sustain and support existing contradictory cultural meanings and values about menopause. I argue that the images continue to misrepresent and define what forms of femininity and sexual gender are desirable and acceptable for menopausal women. The article addresses the problems of gender discrimination and bias within the advertising industry, and illustrates the ways in which readers of visual texts may be influenced by stereotypic assumptions concerning a woman's lived experience of menopause. It illustrates how specific symbolic images directed towards men and women for hormone replacement therapy, testosterone deficiency and sexual dysfunction influence the viewer's decision making and action responses.

Adult↗
PubMed1998

Specificity and duration of neutralizing antibodies induced in healthy cattle after administration of a modified-live virus vaccine against bovine viral diarrhea.

OBJECTIVE: To determine the duration for cross-neutralizing antibodies stimulated by administration of a single dose of a modified-live vaccine against bovine viral diarrhea virus (BVDV) to seronegative cattle. ANIMALS: 23 Angus cows seronegative to BVDV. PROCEDURE: Cows were randomly assigned to control (unvaccinated) or test (vaccinated) groups. Eighteen BVDV-seronegative Angus cattle were vaccinated via IM injection with a modified-live BVDV (NADL strain) vaccine and commingled with 5 unvaccinated seronegative cows. Serum was obtained from the cows before vaccination, on the day of vaccination, and 1.5, 3, 6, 9, 12, and 18 months after vaccination. Serum neutralizing antibody tests were performed on samples obtained at each point after vaccination, using a panel of 12 strains of BVDV that, on the basis of reactivity with monoclonal antibodies, were identified as heterologous. RESULTS: Antibodies against all 12 strains of BVDV (which we tested) were detected by use of viral neutralization testing in samples obtained from vaccinated cattle 18 months after vaccination; however, concentration of antibody for some of the strains was low. Nonvaccinated cattle remained seronegative throughout the 18-month study period. CLINICAL IMPLICATIONS: Analysis of these data indicated that modified-live BVDV vaccines could stimulate an antibody response in seronegative cows that was detectable for at least 18 months after vaccination. These antibodies were able to cross neutralize 12 antigenically diverse strains of BVDV.

Animals↗
PubMed1993

Antiphospholipid syndrome in scleroderma.

Scleroderma has not been described in association with the antiphospholipid syndrome (APS). Only a single manifestation, that of large vessel arterial thrombosis, has been noted in patients with scleroderma and antiphospholipid antibodies. We describe the first case report of a patient with scleroderma and a "full house" for the APS. Clinical suspicion, appropriate investigation and early treatment may help limit the progression of the vasculopathy seen with this syndrome.

Adult↗
PubMed1991

Review of neuromuscular blockers.

Neuromuscular blockers are primarily used as adjuncts in procedures requiring general anesthetics. Some agents have had a long, romantic history while others are relatively new or still in clinical trials. The following is a brief review of the history, mechanism of action, and potential adverse effects of neuromuscular blockers.

Apnea↗
PubMed1991

Amniotic band syndrome: a case report.

A report is presented of a 45 day old female infant with congenital amputation of the great toe, complete constriction bands of the lower leg and fingers all of which are explained by congenital amniotic band syndrome. There is a brief review of the literature on the pathology and possible aetiology.

Amniotic Band Syndrome↗
PubMed1988

The effects of fructose 1,6-diphosphate, caffeine and dantrolene sodium on suxamethonium-induced contractures in denervated rat skeletal muscle.

Previously unidentified forms of suxamethonium-induced contractures have been investigated in chronically denervated rat extensor digitorum longus (EDL) muscle at 20 degrees C. Contractures were assigned to groups 1-6 on the basis of the peak tension (Tp1) during 0-10 min exposure to the drug (3.0 x 10(-5) M), (7.0 x 10(-6) M), and (3.5 x 10(-6) M) and the subsequent retention, increase, or decrease in tension (Tp2), during the further 10 min. It is proposed that four stages exist in the development of contractile changes at 1-7, 8-35, 36-70 and 70-130 days after denervation (DPD) and that contractility is lost at 147 days after denervation. Initial changes, although present in EDL muscles in group 1 at 2.0 DPD s.d. +/- 1 (n = 7) in response to the drug (3.0 x 10(-5) M), were more apparent in EDL muscles in group 2 which were identified at 5.5 DPD s.d. +/- 1.6 (n = 7) by an excessive contracture response (Tp2) to the drug (3.0 x 10(-5) M), 18.3 mN s.d. +/- 10.6. At 5.0 DPD s.d. +/- 2.7 (n = 5) contracture tension (Tp2) was commensurate with membrane depolarization, 13.1 mN/33.1 mV, but residual tension increased to 23.3 mN during the Krebs wash (80 min) whilst membrane depolarization decreased to 9.2 mV. Also, at 4.3 DPD s.d. +/- 2.3 (n = 5) tension (Tp2) increased significantly (P less than or equal to 0.05) in the presence of caffeine (4.1 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Comparison of the mode of action of succinylcholine and succinylmonocholine on rat skeletal muscle after denervation.

The effects of equimolar concentrations (3.0 X 10(-5) M) of succinylcholine (SCh) and succinylmonocholine (SMC) were studied in-vitro at 20 degrees C in rat extensor digitorum longus muscle (EDL) 0-147 days after common peroneal nerve section. Analysis of simultaneous measurements of K+ efflux (mmolL-1 g-1) and contracture tension (mN) to SCh showed that there was a rapid increase in the mean values of both parameters up to 22-28 days after denervation (7.7 mmolL-1 g-1, 36 mN). At the end of the period studied, the contracture response declined to 4.0 mN whilst the capacity for K+ efflux remained relatively high (4.8 mmolL-1 g-1) in comparison with normal contralateral EDL muscle (n = 82) K+ efflux measurements (0.62 mmolL-1 g-1). A significant correlation (r = 0.86, P less than or equal to 0.001) was found between SCh-induced K+ efflux and contracture tension 1-56 days following nerve section which indicated that the development of the contracture response and K+ efflux were concomitant during the period specified. The ratios of maximum contracture tension/K+ efflux in response to SCh and SMC, 18-22 days after denervation were similar, 4.9 and 5.9, respectively. Results indicated that the mode of action of each agent was similar in denervated rat skeletal muscle, and that they were equally potent in their hyperkalaemic potential. Results of comparative measurements of membrane depolarization and contracture tension in response to SCh and SMC showed that both agents produced quantitatively similar responses at 7 and 14 days after denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Lithium and lecithin in tardive dyskinesia: an update.

Psychiatric inpatients with tardive dyskinesia (TD) were treated with either lithium alone (n = 9) or with a combination of lithium and lecithin (n = 9) for 5 weeks in a double-blind, placebo-controlled experiment. A statistically significant but clinically unimportant improvement of TD occurred during both treatments. The addition of lecithin to lithium had no effect.

Clinical Trials as Topic↗
PubMed1978

Nucleosome-associated proteins and phosphoproteins of differentiating Friend erythroleukemia cells.

Mononucleosomes derived from brief digestion of uninduced Friend cell nuclei with micrococcal nuclease contain a set of non-histone chromosomal proteins which are partly or altogether missing in the oligomeric nucleosomes. On the other hand, the latter contain a protein of Mr 190,000 not seen in the mononucleosomes. Longer digestion removes most of these non-histone proteins, excepting the Mr 190,000 protein. Brief digestion of nuclei from Friend cells induced by DMSO or by n-butyrate removes most of the non-histone proteins from the nucleosomes, as did the prolonged digestion of uninduced nuclei. The Mr 190,000 protein remains, while a protein of Mr 27,000 is increased. The rate of phosphorylation of histone H1 associated with mononucleosomes was 3 to 4-fold greater in cells induced with DMSO. The major phosphoprotein and most of the other phosphorylated non-histones were modified at the same rate in control and induced cells. However, a Mr 95,000 protein was less phosphorylated in the induced cells.

Animals↗
PubMed1975

Neuromuscular actions of edrophonium in the lateral segmental tail muscle of the rat in vivo.

The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature endplate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies.

Acetylcholine↗